MicroRNA expression profiles associated with development of drug resistance in Ehrlich ascites tumor cells
Husted, Susanne ; Søkilde, Rolf LU
; Rask, Lene
; Cirera, Susanna
; Busk, Peter Kamp
; Eriksen, Jens
and Litman, Thomas
(2011)
In Molecular Pharmaceutics
8(6).
p.62-2055
- Abstract
Multidrug resistance (MDR) poses a major obstacle to successful chemotherapeutic treatment of cancer, and often involves multiple genes, which may be regulated post-transcriptionally by microRNAs (miRNAs). The purpose of the present study was therefore to identify any resistance-associated changes in miRNA expression in a sensitive and five increasingly drug-resistant Ehrlich ascites tumor (EAT) cell lines, representing different steps in the development of resistance. We used an LNA-enhanced microarray platform to study the global miRNA expression profiles in the six murine EAT cell lines, and identified growth-, hypoxia-, and resistance-specific miRNA patterns. Among the differentially expressed miRNAs, we found the two clusters... (More)
Multidrug resistance (MDR) poses a major obstacle to successful chemotherapeutic treatment of cancer, and often involves multiple genes, which may be regulated post-transcriptionally by microRNAs (miRNAs). The purpose of the present study was therefore to identify any resistance-associated changes in miRNA expression in a sensitive and five increasingly drug-resistant Ehrlich ascites tumor (EAT) cell lines, representing different steps in the development of resistance. We used an LNA-enhanced microarray platform to study the global miRNA expression profiles in the six murine EAT cell lines, and identified growth-, hypoxia-, and resistance-specific miRNA patterns. Among the differentially expressed miRNAs, we found the two clusters miR-183∼miR-96∼miR-182 and miR-200b∼miR-200a∼miR-429 as well as miR-141 to be consistently upregulated in the MDR cell lines, while miR-125b-5p and the two clusters miR-30d∼miR-30b and miR-23b∼miR-27b∼miR-24-1 were downregulated in most of the resistant EAT cells. Several of the target genes for these miRNAs-including Zeb1/Zeb2 and members of the Fox gene family-could contribute to the drug-resistant phenotype, although we did not find that the degree of resistance was directly correlated to any specific changes in miRNA expression. Probably, the observed miRNA expression patterns reflect the underlying genomic instability of the tumor cells, and further studies are needed to explore how the highly complex regulatory miRNA networks contribute to the development of MDR.
(Less)
- author
- Husted, Susanne
; Søkilde, Rolf
LU
; Rask, Lene
; Cirera, Susanna
; Busk, Peter Kamp
; Eriksen, Jens
and Litman, Thomas
- publishing date
- 2011-12-05
- type
- Contribution to journal
- publication status
- published
- keywords
- Animals, Antineoplastic Agents, Carcinoma, Ehrlich Tumor, Cell Line, Tumor, Cisplatin, Doxorubicin, Drug Resistance, Neoplasm, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Mice, MicroRNAs, Reverse Transcriptase Polymerase Chain Reaction, Journal Article, Research Support, Non-U.S. Gov't
- in
- Molecular Pharmaceutics
- volume
- 8
- issue
- 6
- pages
- 8 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:21899346
- scopus:82955240683
- ISSN
- 1543-8392
- DOI
- 10.1021/mp200255d
- language
- English
- LU publication?
- no
- id
- d4530d3c-bba9-45fe-8f0f-7074a753a174
- date added to LUP
- 2017-09-01 14:30:03
- date last changed
- 2024-05-26 21:56:16
@article{d4530d3c-bba9-45fe-8f0f-7074a753a174,
abstract = {{<p>Multidrug resistance (MDR) poses a major obstacle to successful chemotherapeutic treatment of cancer, and often involves multiple genes, which may be regulated post-transcriptionally by microRNAs (miRNAs). The purpose of the present study was therefore to identify any resistance-associated changes in miRNA expression in a sensitive and five increasingly drug-resistant Ehrlich ascites tumor (EAT) cell lines, representing different steps in the development of resistance. We used an LNA-enhanced microarray platform to study the global miRNA expression profiles in the six murine EAT cell lines, and identified growth-, hypoxia-, and resistance-specific miRNA patterns. Among the differentially expressed miRNAs, we found the two clusters miR-183∼miR-96∼miR-182 and miR-200b∼miR-200a∼miR-429 as well as miR-141 to be consistently upregulated in the MDR cell lines, while miR-125b-5p and the two clusters miR-30d∼miR-30b and miR-23b∼miR-27b∼miR-24-1 were downregulated in most of the resistant EAT cells. Several of the target genes for these miRNAs-including Zeb1/Zeb2 and members of the Fox gene family-could contribute to the drug-resistant phenotype, although we did not find that the degree of resistance was directly correlated to any specific changes in miRNA expression. Probably, the observed miRNA expression patterns reflect the underlying genomic instability of the tumor cells, and further studies are needed to explore how the highly complex regulatory miRNA networks contribute to the development of MDR.</p>}},
author = {{Husted, Susanne and Søkilde, Rolf and Rask, Lene and Cirera, Susanna and Busk, Peter Kamp and Eriksen, Jens and Litman, Thomas}},
issn = {{1543-8392}},
keywords = {{Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Cisplatin; Doxorubicin; Drug Resistance, Neoplasm; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Mice; MicroRNAs; Reverse Transcriptase Polymerase Chain Reaction; Journal Article; Research Support, Non-U.S. Gov't}},
language = {{eng}},
month = {{12}},
number = {{6}},
pages = {{62--2055}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Molecular Pharmaceutics}},
title = {{MicroRNA expression profiles associated with development of drug resistance in Ehrlich ascites tumor cells}},
url = {{http://dx.doi.org/10.1021/mp200255d}},
doi = {{10.1021/mp200255d}},
volume = {{8}},
year = {{2011}},
}